107 results on '"Gerlach O."'
Search Results
2. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom
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Spelman, T, primary, Herring, WL, additional, Acosta, C, additional, Hyde, R, additional, Jokubaitis, VG, additional, Pucci, E, additional, Lugaresi, A, additional, Laureys, G, additional, Havrdova, EK, additional, Horakova, D, additional, Izquierdo, G, additional, Eichau, S, additional, Ozakbas, S, additional, Alroughani, R, additional, Kalincik, T, additional, Duquette, P, additional, Girard, M, additional, Petersen, T, additional, Patti, F, additional, Csepany, T, additional, Granella, F, additional, Grand’Maison, F, additional, Ferraro, D, additional, Karabudak, R, additional, Jose Sa, M, additional, Trojano, M, additional, van Pesch, V, additional, Van Wijmeersch, B, additional, Cartechini, E, additional, McCombe, P, additional, Gerlach, O, additional, Spitaleri, D, additional, Rozsa, C, additional, Hodgkinson, S, additional, Bergamaschi, R, additional, Gouider, R, additional, Soysal, A, additional, Castillo-Triviño, T, additional, Prevost, J, additional, Garber, J, additional, de Gans, K, additional, Ampapa, R, additional, Simo, M, additional, Sanchez-Menoyo, JL, additional, Iuliano, G, additional, Sas, A, additional, van der Walt, A, additional, John, N, additional, Gray, O, additional, Hughes, S, additional, De Luca, G, additional, Onofrj, M, additional, Buzzard, K, additional, Skibina, O, additional, Terzi, M, additional, Slee, M, additional, Solaro, C, additional, Oreja-Guevara, C, additional, Ramo-Tello, C, additional, Fragoso, Y, additional, Shaygannejad, V, additional, Moore, F, additional, Rajda, C, additional, Aguera Morales, E, additional, and Butzkueven, H, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Green Synthesis of Gold Nanoparticles Obtained from Algae Sargassum cymosum: Optimization, Characterization and Stability
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Costa, L. H., Hemmer, J.V., Wanderlind, E. H., Gerlach, O. M. S., Santos, A. L. H., Tamanaha, M. S., Bella-Cruz, A., Corrêa, R., Bazani, H. A. G., Radetski, C. M., and Almerindo, G. I.
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- 2020
- Full Text
- View/download PDF
4. Comparative effectiveness in multiple sclerosis: A methodological comparison
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Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, Kalincik, T, Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, and Kalincik, T
- Abstract
BACKGROUND: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. OBJECTIVE: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. METHODS: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. RESULTS: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. CONCLUSIONS: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.
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- 2023
5. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
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Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, MSBase, SG, Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, and MSBase, SG
- Abstract
BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.
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- 2023
6. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
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Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
- Abstract
Background: the prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: to determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: we redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: people who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: this study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by National Health and Medical Research Council of Australia (fellowship nos.1140766 and 1080518, project grant nos. 1129189 and 1083539), the University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), National Institute for Health and Care Research (UK) Advanced Fellowship (grant no. 301728; recipient JWLB) and Academic Clinical Fellowship (grant no. EAN/ACA-006/7488627/C; recipient CD). The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer Schering, Sanofi Genzyme, and Teva. Role of the Funder/Sponsor: The National Health and Medical Research Council of Australia, the University of Melbourne and the National Institute for Health and Care Research (UK) had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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- 2023
7. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis
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Coles, A., Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Alroughani, R., Patti, F., Onofrj, M., Eichau, S., Girard, M., Grand'Maison, F., Yamout, B., Sajedi, S. A., Amato, M. P., Altintas, A., Skibina, O., Grammond, P., Butzkueven, H., Maimone, D., Lechner-Scott, J., Soysal, A., John, N., Gerlach, O., Iuliano, G., Foschi, M., Van Pesch, V., Cartechini, E., Kuhle, J., Sa, M. J., Kermode, A., Gouider, R., Hodgkinson, S., McCombe, P., Sanchez-Menoyo, J. L., Singhal, B., Blanco, Y., Hughes, S., McGuigan, C., Taylor, B., Habek, M., Al-Asmi, A., Mihaela, S., Castillo Trivino, T., Al-Harbi, T., Rojas, J. I., Gray, O., Khurana, D., Van Wijmeersch, B., Kalincik, T., and Brown, J. W. L.
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- 2022
8. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable
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Butler, E., Van Pesch, V., Shalaby, N., Kermode, A., Maimone, D., Blanco, Y., Altintas, A., Turkoglu, R., Butzkueven, H., Van der Walt, A., Skibina, O., Buzzard, K., Lechner-Scott, J., Grammond, P., Khoury, S. J., Yamout, B., Grand'Maison, F., Karabudak, R., Amato, M. P., Terzi, M., Duquette, P., Girard, M., Prat, A., Weinstock-Guttman, B., Lugaresi, A., Onofrj, M., Zakaria, M., Boz, C., Eichau, S., Izquierdo, G., Shaygannejad, V., Alroughani, R., Patti, F., Havrdova, E. K., Horakova, D., Ozakbas, S., Sanchez, M. Martinez, Malpas, C., Simpson-Yap, S., Roos, I., Sharmin, S., Sidhom, Y., Gouider, R., Gerlach, O., Soysal, A., Barnett, M., Kuhle, J., Hughes, S., Sa, M. Jose, and Kalincik, T.
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- 2022
9. Efficacy and persistence between dimethyl fumarate, fingolimod, and ocrelizumab after natalizumab cessation
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Macdonell, R., Zhu, C., Kalincik, T., Horakova, D., Zhen, Z., Buzzard, K., Skibina, O., Alroughani, R., Izquierdo, G., Eichau, S., Kuhle, J., Patti, F., Grand'Maison, F., Hodgkinson, S., Grammond, P., Lechner-Scott, J., Butler, E., Prat, A., Girard, M., Butzkueven, H., Van der Walt, A., Merlo, D., Monif, M., Jokubaitis, V., Khoury, S. J., Yamout, B., Garber, J., Kermode, A., Van Hijfte, L., Laureys, G., Boz, C., Terzi, M., Prevost, J., Gerlach, O., Van Wijmeersch, B., Barnett, M., Van Pesch, V., Sa, M. Jose, Slee, M., Ozakbas, S., Weinstock-Guttman, B., and Duquette, P.
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- 2022
10. Real-World Comparative Effectiveness and Persistence of Cladribine Tablets and Other Oral Disease-Modifying Treatments for Multiple Sclerosis from GLIMPSE: Results from the MSBase Registry
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Spitaleri, D., Kuhle, J., Ozakbas, SERKAN, Patti, F., Ampapa, R., Horakova, D., Soysal, A., Butzkueven, H., Spelman, T., Lechner-Scott, J., Yamout, B., Alroughani, R., Terzi, M., Hodgkinson, S., Sanchez-Menoyo, J., Blanco, Y., Van Pesch, V., Van der Walt, A., Kalincik, T., Laureys, G., Wong, S., Tundia, N., Altintas, A., Oh, J., Gerlach, O., Al-Asmi, A., and Macdonell, R.
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- 2022
11. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.
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Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Izquierdo G., Eichau S., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B.I., Karabudak R., Gerlach O., Lechner-Scott J., Maimone D., Bergamaschi R., Van Pesch V., Iuliano G., Cartechini E., JosA Sa M., Ampapa R., Barnett M., Hughes S.E., Ramo-Tello C.M., Hodgkinson S., Spitaleri D.L.A., Petersen T., Butler E.G., Slee M., McGuigan C., McCombe P.A., Granella F., Cristiano E., Prevost J., Taylor B.V., Sa Nchez-Menoyo J.L., Laureys G., Van Hijfte L., Vucic S., Macdonell R.A., Gray O., Olascoaga J., Deri N., Fragoso Y.D., Shaw C., Kalincik T., Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Izquierdo G., Eichau S., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B.I., Karabudak R., Gerlach O., Lechner-Scott J., Maimone D., Bergamaschi R., Van Pesch V., Iuliano G., Cartechini E., JosA Sa M., Ampapa R., Barnett M., Hughes S.E., Ramo-Tello C.M., Hodgkinson S., Spitaleri D.L.A., Petersen T., Butler E.G., Slee M., McGuigan C., McCombe P.A., Granella F., Cristiano E., Prevost J., Taylor B.V., Sa Nchez-Menoyo J.L., Laureys G., Van Hijfte L., Vucic S., Macdonell R.A., Gray O., Olascoaga J., Deri N., Fragoso Y.D., Shaw C., and Kalincik T.
- Abstract
BACKGROUND AND OBJECTIVES: The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, ultraviolet B radiation exposure (UVB) and the severity of MS. METHOD(S): This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and >=1 EDSS [Expanded Disability Status Scale] score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from NASA's Total Ozone Mapping Spectrometer) at ages 6 and 18 and the year of disability assessment were calculated. Disease severity was quantified with MS Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB and MSSS. RESULT(S): 46,128 patients contributing 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2+/-12, resident between latitudes 19degree35' and 56degree16') were included in this study. Latitude showed a non-linear association with MS severity. In latitudes greater than 40degree, more severe disease was associated with higher latitudes (beta=0.08, 95%CI: 0.04 to 0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40degree (beta=-0.02, 95% CI:-0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 (beta=- 0.5, 95% CI: -0.6 to 0.4) and 18 years (beta=- 0.6, 95%CI:-0.7 to 0.4), as well as with lower life-time UVB exposure at the time of disability assessment (be
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- 2022
12. Confirmed disability progression as a marker of permanent disability in multiple sclerosis.
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Sharmin S., Bovis F., Malpas C., Horakova D., Havrdova E., Izquierdo G., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Gerlach O., Alroughani R., Boz C., Shaygannejad V., van Pesch V., Cartechini E., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Iuliano G., Granella F., Van Wijmeersch B., Spitaleri D., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J., Soysal A., Vucic S., Petersen T., de Gans K., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Castillo-Trivino T., Saladino M., Barnett M., Moore F., Rozsa C., Yamout B., Skibina O., van der Walt A., Buzzard K., Gray O., Hughes S., Sempere A.P., Singhal B., Fragoso Y., Shaw C., Kermode A., Taylor B., Simo M., Shuey N., Al-Harbi T., Macdonell R., Dominguez J.A., Csepany T., Sirbu C., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Malpas C., Horakova D., Havrdova E., Izquierdo G., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Gerlach O., Alroughani R., Boz C., Shaygannejad V., van Pesch V., Cartechini E., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Iuliano G., Granella F., Van Wijmeersch B., Spitaleri D., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J., Soysal A., Vucic S., Petersen T., de Gans K., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Castillo-Trivino T., Saladino M., Barnett M., Moore F., Rozsa C., Yamout B., Skibina O., van der Walt A., Buzzard K., Gray O., Hughes S., Sempere A.P., Singhal B., Fragoso Y., Shaw C., Kermode A., Taylor B., Simo M., Shuey N., Al-Harbi T., Macdonell R., Dominguez J.A., Csepany T., Sirbu C., Sormani M.P., Butzkueven H., and Kalincik T.
- Abstract
Background and purpose: The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Method(s): In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Result(s): The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score >1.5). Conclusion(s): Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.Copyright © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behal
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- 2022
13. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis.
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Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., Kalincik T., Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., and Kalincik T.
- Abstract
OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHOD(S): This was a retrospective cohort study from two large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12-months were included in the analysis. The primary study outcome was annualised relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULT(S): 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for seven therapies. Annualised rates of relapse (ARR) started to increase 2-months after natalizumab cessation (month 2-4 ARR, 95% confidence interval): 0.47, 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89), and stabilised faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01-0.29). Magnitude of disease reactivation for other therapies was low, but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were higher relapse rate in the year before cessation, female sex, younger age and higher EDSS. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95%CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). CONCLUSION(S): The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different t
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- 2022
14. Confirmed disability progression as a marker of permanent disability in multiple sclerosis
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Sharmin, S., Bovis, F., Malpas, C., Horakova, D., Havrdova, E.K., Izquierdo, G., Eichau, S., Trojano, M., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand'Maison, F., Grammond, P., Sola, P., Ferraro, D., Terzi, M., Gerlach, O., Alroughani, R., Boz, C., Shaygannejad, V., van Pesch, V., Cartechini, E., Kappos, L., Lechner‐Scott, J., Bergamaschi, R., Turkoglu, R., Solaro, C., Iuliano, G., Granella, F., Van Wijmeersch, B., Spitaleri, D., Slee, M., McCombe, P., Prevost, J., Ampapa, R., Ozakbas, S., Sanchez‐Menoyo, J.L., Soysal, A., Vucic, S., Petersen, T., de Gans, K., Butler, E., Hodgkinson, S., Sidhom, Y., Gouider, R., Cristiano, E., Castillo‐Triviño, T., Saladino, M.L., Barnett, M., Moore, F., Rozsa, C., Yamout, B., Skibina, O., van der Walt, A., Buzzard, K., Gray, O., Hughes, S., Sempere, A.P., Singhal, B., Fragoso, Y., Shaw, C., Kermode, A., Taylor, B., Simo, M., Shuey, N., Al‐Harbi, T., Macdonell, R., Dominguez, J.A., Csepany, T., Sirbu, C.A., Sormani, M.P., Butzkueven, H., Kalincik, T., Sharmin, S., Bovis, F., Malpas, C., Horakova, D., Havrdova, E.K., Izquierdo, G., Eichau, S., Trojano, M., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand'Maison, F., Grammond, P., Sola, P., Ferraro, D., Terzi, M., Gerlach, O., Alroughani, R., Boz, C., Shaygannejad, V., van Pesch, V., Cartechini, E., Kappos, L., Lechner‐Scott, J., Bergamaschi, R., Turkoglu, R., Solaro, C., Iuliano, G., Granella, F., Van Wijmeersch, B., Spitaleri, D., Slee, M., McCombe, P., Prevost, J., Ampapa, R., Ozakbas, S., Sanchez‐Menoyo, J.L., Soysal, A., Vucic, S., Petersen, T., de Gans, K., Butler, E., Hodgkinson, S., Sidhom, Y., Gouider, R., Cristiano, E., Castillo‐Triviño, T., Saladino, M.L., Barnett, M., Moore, F., Rozsa, C., Yamout, B., Skibina, O., van der Walt, A., Buzzard, K., Gray, O., Hughes, S., Sempere, A.P., Singhal, B., Fragoso, Y., Shaw, C., Kermode, A., Taylor, B., Simo, M., Shuey, N., Al‐Harbi, T., Macdonell, R., Dominguez, J.A., Csepany, T., Sirbu, C.A., Sormani, M.P., Butzkueven, H., and Kalincik, T.
- Abstract
Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29–0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.
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- 2022
15. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis
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Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, Kalincik, T, Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, and Kalincik, T
- Abstract
BACKGROUND AND OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHODS: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULTS: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). DISCUSSION: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued di
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- 2022
16. Multiple Sclerosis Severity Score (MSSS) improves the accuracy of individualized prediction in MS
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Kalincik, T, Kister, I, Bacon, TE, Malpas, CB, Sharmin, S, Horakova, D, Kubala-Havrdova, E, Patti, F, Izquierdo, G, Eichau, S, Ozakbas, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Sola, P, Ferraro, D, Alroughani, R, Terzi, M, Boz, C, Grand'Maison, F, Bergamaschi, R, Gerlach, O, Sa, MJ, Kappos, L, Cartechini, E, Lechner-Scott, J, van Pesch, V, Shaygannejad, V, Granella, F, Spitaleri, D, Iuliano, G, Maimone, D, Prevost, J, Soysal, A, Turkoglu, R, Ampapa, R, Butzkueven, H, Cutter, G, Kalincik, T, Kister, I, Bacon, TE, Malpas, CB, Sharmin, S, Horakova, D, Kubala-Havrdova, E, Patti, F, Izquierdo, G, Eichau, S, Ozakbas, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Sola, P, Ferraro, D, Alroughani, R, Terzi, M, Boz, C, Grand'Maison, F, Bergamaschi, R, Gerlach, O, Sa, MJ, Kappos, L, Cartechini, E, Lechner-Scott, J, van Pesch, V, Shaygannejad, V, Granella, F, Spitaleri, D, Iuliano, G, Maimone, D, Prevost, J, Soysal, A, Turkoglu, R, Ampapa, R, Butzkueven, H, and Cutter, G
- Abstract
BACKGROUND: The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. OBJECTIVE: To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. METHODS: The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients' demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. RESULTS: A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. CONCLUSION: Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.
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- 2022
17. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry
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Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, Butzkueven, H, Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, and Butzkueven, H
- Abstract
BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.
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- 2022
18. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: results from MSBase registry
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Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Spelman, T.; Ozakbas, S.; Alroughani, R.; Terzi, M.; Hodgkinson, S.; Laureys, G.; Kalincik, T.; Van Der Walt, A.; Yamout, B.; Lechner-Scott, J.; Soysal, A.; Kuhle, J.; Sanchez-Menoyo, J.L.; Blanco Morgado, Y.; Spitaleri, D.; van Pesch, V.; Horakova, D.; Ampapa, R.; Patti, F.; Macdonell, R.; Al-Asmi, A.; Gerlach, O.; Oh, J.; Tundia, N.; Wong, S.L.; Butzkueven, H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Spelman, T.; Ozakbas, S.; Alroughani, R.; Terzi, M.; Hodgkinson, S.; Laureys, G.; Kalincik, T.; Van Der Walt, A.; Yamout, B.; Lechner-Scott, J.; Soysal, A.; Kuhle, J.; Sanchez-Menoyo, J.L.; Blanco Morgado, Y.; Spitaleri, D.; van Pesch, V.; Horakova, D.; Ampapa, R.; Patti, F.; Macdonell, R.; Al-Asmi, A.; Gerlach, O.; Oh, J.; Tundia, N.; Wong, S.L.; Butzkueven, H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
- Abstract
Background: effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. Objectives: use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. Methods: retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). Results: cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. Conclusion: cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators., Financial support for this study was provided entirely by a contract with EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100004755). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: NT and SLW.
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- 2022
19. Personality traits are not associated with changes in employment status over 3 years in persons with multiple sclerosis
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Van Der Hiele, K, Van Egmond, Eea, Van Gorp, Dam, Jongen, Pj, Reneman, Mf, van der Klink, J., Beenakker, Eac, Van Eijk, Jjj, Frequin, Stfm, Hoitsma, E, Gerlach, O., Mostert, Jp, Verhagen, Wim, Heerings, Map, Middelkoop, Ham, Visser, Lh, Van Der Hiele, K, Van Egmond, Eea, Van Gorp, Dam, Jongen, Pj, Reneman, Mf, van der Klink, J., Beenakker, Eac, Van Eijk, Jjj, Frequin, Stfm, Hoitsma, E, Gerlach, O., Mostert, Jp, Verhagen, Wim, Heerings, Map, Middelkoop, Ham, and Visser, Lh
- Abstract
Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions.
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- 2022
20. Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression (vol 208, 106180, 2021)
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De Brouwer, E, Becker, T, Moreau, Y, Havrdova, EK, Trojano, M, Eichau, S, Ozakbas, S, Onofrj, M, Grammond, P, Kuhle, J, Kappos, L, Sola, P, Cartechini, E, Lechner-Scott, J, Alroughani, R, Gerlach, O, Kalincik, T, Granella, F, Grand'Maison, F, Bergamaschi, R, Sa, MJ, Van Wijmeersch, B, Soysal, A, Sanchez-Menoyo, JL, Solaro, C, Boz, C, Iuliano, G, Buzzard, K, Aguera-Morales, E, Terzi, M, Trivio, TC, Spitaleri, D, Van Pesch, V, Shaygannejad, V, Moore, F, Oreja-Guevara, C, Maimone, D, Gouider, R, Csepany, T, Ramo-Tello, C, and Peeters, L
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- 2022
21. Work difficulties in people with multiple sclerosis: the role of depression, anxiety and coping
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van Egmond, E., van der Hiele, K., van Gorp, D., Jongen, S., van der Klink, J., Reneman, M., Beenakker, M., van Eijk, J., Frequin, S., de Gans, K., van Geel, B., Gerlach, O., Hengstman, G., Mostert, J., Verhagen, W., Middelkoop, H., Visser, L., and Extremities Pain and Disability (EXPAND)
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- 2021
22. Personality traits are not associated with changes in employment status over 3 years in persons with multiple sclerosis.
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van der Hiele, K., van Egmond, E. E. A., van Gorp, D. A. M., Jongen, P. J., Reneman, M. F., van der Klink, J. J. L., Beenakker, E. A. C., van Eijk, J. J. J., Frequin, S. T. F. M., Hoitsma, E., Gerlach, O. H. H., Mostert, J. P., Verhagen, W. I. M., Heerings, M. A. P., Middelkoop, H. A. M., and Visser, L. H.
- Abstract
Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
- View/download PDF
23. Disability accrual in primary-progressive & secondaryprogressive multiple sclerosis.
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Boz C., Diouf I., Malpas C., Nguyen A.-L., Moradi N., Horakova D., Kubala Havrdova E., Patti F., Izquierdo G., Eichau S., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Weinstock-Guttman B., Amato M.P., Grammond P., Gerlach O., Ozakbas S., Sola P., Ferraro D., Butzkueven H., Lechner-Scott J., Alroughani R., Van Pesch V., Cartechini E., Terzi M., Maimone D., Ramo-Tello C., Spitaleri D., Kappos L., Yamout B., Sa M., Slee M., Blanco Y., Bergamaschi R., Butler E., Iuliano G., Granella F., Sidhom Y., Gouider R., Ampapa R., Van Wijmeersch B., Karabudak R., Prevost J., Sanchez-Menoyo J.L., Verheul F., Mccombe P., Castillo-Trivino T., Macdonell R., Altintas A., Laureys G., Van Hijfte L., Van Der Walt A., Vucic S., Turkoglu R., Barnett M., Cristiano E., Zakaria M., Shaygannejad V., Hodgkinson S., Soysal A., Kalincik T., Harding-Forrester S., Roos I., Sharmin S., Boz C., Diouf I., Malpas C., Nguyen A.-L., Moradi N., Horakova D., Kubala Havrdova E., Patti F., Izquierdo G., Eichau S., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Weinstock-Guttman B., Amato M.P., Grammond P., Gerlach O., Ozakbas S., Sola P., Ferraro D., Butzkueven H., Lechner-Scott J., Alroughani R., Van Pesch V., Cartechini E., Terzi M., Maimone D., Ramo-Tello C., Spitaleri D., Kappos L., Yamout B., Sa M., Slee M., Blanco Y., Bergamaschi R., Butler E., Iuliano G., Granella F., Sidhom Y., Gouider R., Ampapa R., Van Wijmeersch B., Karabudak R., Prevost J., Sanchez-Menoyo J.L., Verheul F., Mccombe P., Castillo-Trivino T., Macdonell R., Altintas A., Laureys G., Van Hijfte L., Van Der Walt A., Vucic S., Turkoglu R., Barnett M., Cristiano E., Zakaria M., Shaygannejad V., Hodgkinson S., Soysal A., Kalincik T., Harding-Forrester S., Roos I., and Sharmin S.
- Abstract
Background: Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS. Objective(s): We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016). Method(s): Inclusion required adult-onset progressive MS; >= 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS <= 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if >= 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over >= 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS >= 7 (wheelchair required) was assessed (Kaplan-Meier). Result(s): 5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 +/- 10.2, vs. 41.5 +/- 10.7 [mean +/- SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78-0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98-0.99); and higher in males (1.18; 1.12-1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71
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- 2021
24. Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression
- Author
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De Brouwer, E, Becker, T, Moreau, Y, Havrdova, EK, Trojano, M, Eichau, S, Ozakbas, S, Onofrj, M, Grammond, P, Kuhle, J, Kappos, L, Sola, P, Cartechini, E, Lechner-Scott, J, Alroughani, R, Gerlach, O, Kalincik, T, Granella, F, Grand'Maison, F, Bergamaschi, R, Sa, MJ, Van Wijmeersch, B, Soysal, A, Luis Sanchez-Menoyo, J, Solaro, C, Boz, C, Iuliano, G, Buzzard, K, Aguera-Morales, E, Terzi, M, Castillo Trivio, T, Spitaleri, D, Van Pesch, V, Shaygannejad, V, Moore, F, Oreja-Guevara, C, Maimone, D, Gouider, R, Csepany, T, Ramo-Tello, C, Peeters, L, De Brouwer, E, Becker, T, Moreau, Y, Havrdova, EK, Trojano, M, Eichau, S, Ozakbas, S, Onofrj, M, Grammond, P, Kuhle, J, Kappos, L, Sola, P, Cartechini, E, Lechner-Scott, J, Alroughani, R, Gerlach, O, Kalincik, T, Granella, F, Grand'Maison, F, Bergamaschi, R, Sa, MJ, Van Wijmeersch, B, Soysal, A, Luis Sanchez-Menoyo, J, Solaro, C, Boz, C, Iuliano, G, Buzzard, K, Aguera-Morales, E, Terzi, M, Castillo Trivio, T, Spitaleri, D, Van Pesch, V, Shaygannejad, V, Moore, F, Oreja-Guevara, C, Maimone, D, Gouider, R, Csepany, T, Ramo-Tello, C, and Peeters, L
- Abstract
BACKGROUND AND OBJECTIVES: Research in Multiple Sclerosis (MS) has recently focused on extracting knowledge from real-world clinical data sources. This type of data is more abundant than data produced during clinical trials and potentially more informative about real-world clinical practice. However, this comes at the cost of less curated and controlled data sets. In this work we aim to predict disability progression by optimally extracting information from longitudinal patient data in the real-world setting, with a special focus on the sporadic sampling problem. METHODS: We use machine learning methods suited for patient trajectories modeling, such as recurrent neural networks and tensor factorization. A subset of 6682 patients from the MSBase registry is used. RESULTS: We can predict disability progression of patients in a two-year horizon with an ROC-AUC of 0.85, which represents a 32% decrease in the ranking pair error (1-AUC) compared to reference methods using static clinical features. CONCLUSIONS: Compared to the models available in the literature, this work uses the most complete patient history for MS disease progression prediction and represents a step forward towards AI-assisted precision medicine in MS.
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- 2021
25. Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis
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Mimpen, M, Muris, AH, Rolf, L, Gerlach, O, Kuhle, J, Hupperts, R, Smolders, Joost, Damoiseaux, J, Mimpen, M, Muris, AH, Rolf, L, Gerlach, O, Kuhle, J, Hupperts, R, Smolders, Joost, and Damoiseaux, J
- Abstract
Background and purpose: Natural killer (NK) cells may play a role in multiple sclerosis (MS). Ratios of NK cells to CD4+ T cells have been proposed as a biomarker for the therapeutic effect of stem cell transplantation in MS. The objectives here were to explore the relevance of this ratio in MS patients by analysing NK and T cell subsets, as well as their prognostic value for disease activity. Methods: Baseline peripheral blood mononuclear cells of 50 relapsing–remitting MS patients, participating in our vitamin D supplementation study (SOLARIUM), were analysed with flow cytometry. Disease activity was measured as new magnetic resonance imaging lesions, relapses and mean plasma neurofilament light chain levels after 48 weeks of follow-up. Results: The proportion of NK cells correlated negatively with CD4+ T cells (R = −0.335, p = 0.001) and interleukin 17A (IL-17A+) CD4+ T cells (R = −0.203, p = 0.043). Participants with magnetic resonance imaging activity or relapses displayed lower NK/IL-17A+CD4+ T cell ratios (p =0.025 and p = 0.006, respectively). The NK/IL-17A+CD4+ T cell ratio correlated negatively with neurofilament light chain levels (R = −0.320, p = 0.050). Vitamin D supplementation did not affect these ratios. Conclusions: Our data suggest a protective role of an expanded NK cell compartment compared to the CD4+ T cell subset fractions in relapsing–remitting MS patients. NK/CD4+ T cell ratios may be a prognostic biomarker for disease activity in MS.
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- 2021
26. Synthesis of nanostructured lean-NO x catalysts by direct laser deposition of monometallic Pt-, Rh- and bimetallic PtRh-nanoparticles on SiO2 support
- Author
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Savastenko, N., Volpp, H.-R., Gerlach, O., and Strehlau, W.
- Published
- 2008
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27. Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis
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Mimpen, M. (Max), Muris, A.-H. (Anne-Hilde), Rolf, L. (Linda), Gerlach, O. (Oliver), Kuhle, J. (Jens), Hupperts, R. (Raymond), Smolders, J. (Joost), Damoiseaux, J., Mimpen, M. (Max), Muris, A.-H. (Anne-Hilde), Rolf, L. (Linda), Gerlach, O. (Oliver), Kuhle, J. (Jens), Hupperts, R. (Raymond), Smolders, J. (Joost), and Damoiseaux, J.
- Abstract
Background and purpose: Natural killer (NK) cells may play a role in multiple sclerosis (MS). Ratios of NK cells to CD4+ T cells have been proposed as a biomarker for the therapeutic effect of stem cell transplantation in MS. The objectives here were to explore the relevance of this ratio in MS patients by analysing NK and T cell subsets, as well as their prognostic value for disease activity. Methods: Baseline peripheral bloo
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- 2020
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28. Measurement of the controlled variable during heating of Ti6Al4V for thixoforging
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Gerlach, O, primary, Lechler, A, additional, and Verl, A, additional
- Published
- 2018
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29. Funktionale Programmiersprachen zur Entwicklung numerischer Steuerungen*/Use of functional programming languages for developing computerized numerical controls - Analysis of their potential and fields of application
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Gerlach, O., primary, Csiszar, A., additional, Lechler, A., additional, and Verl, A. Prof., additional
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- 2017
- Full Text
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30. Semi-solid Formgebung von AMC-Werkstoffen
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Seyboldt, C., Liewald, M., Schubert, T., Weißgärber, T., Gerlach, O., Lechler, A., and Publica
- Abstract
Hinsichtlich der Verarbeitung von partikelverstärkten Aluminiummatrix-Verbundwerkstoffen (AMC) zu komplexen Bauteilen mit hoher Endkonturnähe, Maßhaltigkeit und hervorragenden mechanischen Eigenschaften bietet die Formgebung im teilflüssigen Zustand aussichtsreiche Perspektiven. In diesem Zusammenhang beschreibt der Fachbeitrag eine neuentwickelte Prozessroute zur Herstellung von Hochleistungskomponenten aus solchen AMC-Werkstoffen und zeigt deren Potentiale auf.
- Published
- 2015
31. Attitude stabilization and control of earth satellites
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Gerlach, O. H.
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- 1965
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32. Semi-solid Formgebung von AMC-Werkstoffen*/Semi-solid forming of AMC materials - Potential of a new process flow for high performance components
- Author
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Seyboldt, C., primary, Schubert, T., additional, Gerlach, O., additional, Liewald, M., additional, Weißgärber, T., additional, and Lechler, A., additional
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- 2015
- Full Text
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33. Time constant measurement for control of induction heating processes for thixoforming
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Gerlach, O, primary, Lechler, A, additional, and Verl, A, additional
- Published
- 2014
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34. Von der nachholenden zur nachhaltigen Entwicklung - und wieder zurück. Vom Schicksal der Naturverhältnisse in der Entwicklungsdiskussion
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Gerlach, O., Kalmring, S., Kumitz, D., Nowak, A., Görg, Christoph, Gerlach, O., Kalmring, S., Kumitz, D., Nowak, A., and Görg, Christoph
- Published
- 2004
35. Die Wirkung von »Entspannungsmusik« auf Patienten, Ärzte und Pflegepersonal einer internistischen Intensivstation
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Neuhof, H., primary, Klapp, B. F., additional, Gerlach, O., additional, Koch, H. U., additional, Hundhausen, T., additional, and Lasch, H. G., additional
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- 2008
- Full Text
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36. Synthesis of nanostructured lean-NO x catalysts by direct laser deposition of monometallic Pt-, Rh- and bimetallic PtRh-nanoparticles on SiO2 support
- Author
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Savastenko, N., primary, Volpp, H.-R., additional, Gerlach, O., additional, and Strehlau, W., additional
- Published
- 2007
- Full Text
- View/download PDF
37. GABAB receptors at glutamatergic synapses in the rat striatum
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Lacey, C.J., primary, Boyes, J., additional, Gerlach, O., additional, Chen, L., additional, Magill, P.J., additional, and Bolam, J.P., additional
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- 2005
- Full Text
- View/download PDF
38. Book reviews
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Wittenberg, H. and Gerlach, O. H.
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- 1966
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39. Comparison of multiple disease modifying therapies in multiple sclerosis with marginal structural models
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Diouf, I., Malpas, C., Sharmin, S., Izanne Roos, Horakova, D., Havrdova, E. K., Patti, F., Shaygannejad, V., Ozakbas, S., Izquierdo, G., Eichau, S., Onofrj, M., Lugaresi, A., Alroughani, R., Duquette, P., Terzi, M., Boz, C., Grand Maison, F., Hamdy, S., Sola, P., Grammond, P., Turkoglu, R., Skibina, O., Buzzard, K., Yamout, B., Altintas, A., Gerlach, O., Pesch, V., Blanco, Y., Maimone, D., Lechner-Scott, J., Bergamaschi, R., Karabudak, R., Barnet, M., Hughes, S., Sa, M. J., Kappos, L., Hodgkinson, S., Butzkueven, H., Prevost, J., Laureys, G., Moore, F., and Kalincik, T.
40. Disease reactivation after cessation of disease-modifying therapy in relapsing-remitting multiple sclerosis
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Izanne Roos, Malpas, C., Leray, E., Casey, R., Horakova, D., Havrdova, E. Kubala, Debouverie, M., Patti, F., Seze, J., Izquierdo, G., Eichau, S., Edan, G., Prat, A., Girard, M., Ozakbas, S., Grammond, P., Zephir, H., Ciron, J., Maillart, E., Moreau, T., Amato, M. P., Labauge, P., Alroughani, R., Buzzard, K., Skibina, O., Terzi, M., Laplaud, D., Berger, E., Grand Maison, F., Lebrun-Frenay, C., Cartechini, E., Boz, C., Lechner-Scott, J., Clavelou, P., Stankoff, B., Prevost, J., Kappos, L., Pelletier, J., Shaygannejad, V., Yamout, B., Gerlach, O., Spitaleri, D., Pesch, V., Gout, O., Turkoglu, R., Heinzlef, O., Thouvenot, E., Vukusic, S., Butzkueven, H., and Kalincik, T.
41. Disability accrual in primary-progressive & secondary-progressive multiple sclerosis
- Author
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Harding-Forrester, S., Izanne Roos, Sharmin, S., Diouf, I., Malpas, C., Nguyen, A. -L, Moradi, N., Horakova, D., Havrdova, E. Kubala, Patti, F., Izquierdo, G., Eichau, S., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand Maison, F., Weinstock-Guttman, B., Amato, M. P., Grammond, P., Gerlach, O., Ozakbas, S., Sola, P., Ferraro, D., Butzkueven, H., Lechner-Scott, J., Boz, C., Alroughani, R., Pesch, V., Cartechini, E., Terzi, M., Maimone, D., Ramo-Tello, C., Spitaleri, D., Kappos, L., Yamout, B., Sa, M., Slee, M., Blanco, Y., Bergamaschi, R., Butler, E., Iuliano, G., Granella, F., Sidhom, Y., Gouider, R., Ampapa, R., Wijmeersch, B., Karabudak, R., Prevost, J., Sanchez-Menoyo, J. L., Verheul, F., Mccombe, P., Castillo-Trivino, T., Macdonell, R., Altintas, A., Laureys, G., Hijfte, L., Walt, A., Vucic, S., Turkoglu, R., Barnett, M., Cristiano, E., Zakaria, M., Shaygannejad, V., Hodgkinson, S., Soysal, A., and Kalincik, T.
42. High and low efficacy therapy in secondary progressive multiple sclerosis after accounting for therapeutic lag
- Author
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Roos, I., Emmanuelle Leray, Romain Casey, Horakova, D., Kubala Havrdova, E., Izquierdo, G., Eichau Madueno, S., Patti, F., Edan, G., Marc Debouverie, Jean Pelletier, Ozakbas, S., Amato, M. P., Pierre Clavelou, Grammond, P., Boz, C., Jonathan Ciron, Gerlach, O., Grand Maison, F., Lechner-Scott, J., Malpas, C., Butzkueven, H., Vukusic, S., Kalincik, T., Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Charles University [Prague] (CU), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Timone [CHU - APHM] (TIMONE), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), Università degli Studi di Firenze = University of Florence (UniFI), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Zuyderland Hospital [Heerlen, The Netherlands], Monash University [Clayton], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), and CHU Toulouse [Toulouse]
- Subjects
[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
43. Developments in mathematical models of human pilot behaviour
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Gerlach, O. H., primary
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- 1977
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44. Simulation research: role of university, government and industry in the Netherlands
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Gerlach, O. H., primary
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- 1980
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45. System der Finanzwissenschaft.
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Bastable, C. F., primary, Roscher, Wilhelm, additional, and Gerlach, O., additional
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- 1902
- Full Text
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46. ChemInform Abstract: OXIDATIVE DIMERISIERUNG ELEKTRONENREICHER ALKENE
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EFFENBERGER, F., primary and GERLACH, O., additional
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- 1970
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47. Determination of Performance and Stability Parameters from Nonsteady Flight Test Maneuvers
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Gerlach, O. H., primary
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- 1970
- Full Text
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48. Ueber die Brommesaconsäure
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Lossen, W., primary and Gerlach, O., additional
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- 1894
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49. Oxidative dimerization of electron-rich alkenes
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Effenberger, F., primary and Gerlach, O., additional
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- 1970
- Full Text
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50. GABAB receptors at glutamatergic synapses in the rat striatum
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Lacey, C.J., Boyes, J., Gerlach, O., Chen, L., Magill, P.J., and Bolam, J.P.
- Subjects
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GABA , *NEURAL transmission , *NEURAL circuitry , *IMMUNOGLOBULINS , *CELL membranes - Abstract
Abstract: Although multiple effects of GABAB receptor activation on synaptic transmission in the striatum have been described, the precise locations of the receptors mediating these effects have not been determined. To address this issue, we carried out pre-embedding immunogold electron microscopy in the rat using antibodies against the GABAB receptor subunits, GABAB1 and GABAB2. In addition, to investigate the relationship between GABAB receptors and glutamatergic striatal afferents, we used antibodies against the vesicular glutamate transporters, vesicular glutamate transporter 1 and vesicular glutamate transporter 2, as markers for glutamatergic terminals. Immunolabeling for GABAB1 and GABAB2 was widely and similarly distributed in the striatum, with immunogold particles localized at both presynaptic and postsynaptic sites. The most commonly labeled structures were dendritic shafts and spines, as well as terminals forming asymmetric and symmetric synapses. In postsynaptic structures, the majority of labeling associated with the plasma membrane was localized at extrasynaptic sites, although immunogold particles were also found at the postsynaptic specialization of some symmetric, putative GABAergic synapses. Labeling in axon terminals was located within, or at the edge of, the presynaptic active zone, as well as at extrasynaptic sites. Double labeling for GABAB receptor subunits and vesicular glutamate transporters revealed that labeling for both GABAB1 and GABAB2 was localized on glutamatergic axon terminals that expressed either vesicular glutamate transporter 1 or vesicular glutamate transporter 2. The patterns of innervation of striatal neurons by the vesicular glutamate transporter 1- and vesicular glutamate transporter 2-positive terminals suggest that they are selective markers of corticostriatal and thalamostriatal afferents, respectively. These results thus provide evidence that presynaptic GABAB heteroreceptors are in a position to modulate the two major excitatory inputs to striatal spiny projection neurons arising in the cortex and thalamus. In addition, presynaptic GABAB autoreceptors are present on the terminals of spiny projection neurons and/or striatal GABAergic interneurons. Furthermore, the data indicate that GABA may also affect the excitability of striatal neurons via postsynaptic GABAB receptors. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
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